No abstract

Frailty is a common condition in older persons and has been described as a geriatric syndrome resulting from age-related cumulative declines across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to resist stress. Therefore, frailty is considered as a state of high vulnerability for adverse health outcomes, such as disability, falls, hospitalization, institutionalization, and mortality. Regular physical activity has been shown to protect against diverse components of the frailty syndrome in men and women of all ages and frailty is not a contra-indication to physical activity, rather it may be one of the most important reasons to prescribe physical exercise. It has been recognized that physical activity can have an impact on different components of the frailty syndrome. This review will address the role of physical activity on the most relevant components of frailty syndrome, with specific reference to: (i) sarcopenia, as a condition which frequently overlaps with frailty; (ii) functional impairment, considering the role of physical inactivity as one of the strongest predictors of physical disability in elders; (iii) cognitive performance, including evidence on how exercise and physical activity decrease the risk of early cognitive decline and poor cognition in late life; and (iv) depression by reviewing the effect of exercise on improving mood and increasing positive well-being.

Resveratrol (Res) has been reported to possess cancer chemopreventive activity on the basis of its in vitro effects on tumor cells and in vivo experimental models of rodents transplanted with parental tumors or treated with carcinogens. We investigated the effects of Res on the development of mammary tumors appearing spontaneously in HER-2/neu transgenic mice at an early age. The mechanisms involved in the Res antitumor effect were evaluated by studying the immune effectiveness, tumor apoptosis and expression of mRNA and protein for HER-2/neu in tumoral mammary glands from Res-treated mice and in tumor cell lines. Res supplementation delayed the development of spontaneous mammary tumors (p < 0.001), reduced the mean number and size of mammary tumors (p < 0.0001) and diminished the number of lung metastases in HER-2/neu transgenic mice. The effects of Res were associated with downregulation of HER-2/neu gene expression and increased apoptosis both in tumoral mammary glands and in murine (N202) and human (SKBr3) tumor cell lines. Neither the basal, the IL-2-induced NK activity nor the lymphocyte number and proliferation was modified in Res-supplemented compared to control mice. Our results demonstrate that Res supplementation delays the development and reduces the metastasizing capacity of spontaneous mammary tumors in HER-2/neu transgenic mice. The antitumor effect of Res might be related to the downregulation of HER-2/neu expression and the induction of apoptosis in tumor cells. ' 2005 Wiley-Liss, Inc.Key words: resveratrol; HER-2/neu; mammary tumor; transgenic mouse; apoptosis Cancer chemoprevention, the prevention of cancer by chemical agents that reduce the risk of carcinogenesis, is one of the most direct ways to reduce morbidity and mortality. Res (trans-3,4 0 , 5-trihydroxystilbene) is a naturally occurring polyphenolic antioxidant compound present in grapes, mulberries, peanuts and red wine. It has been identified as an excellent candidate cancer chemopreventive, based on its safety and efficacy in experimental models of carcinogenesis. It has been found to inhibit diverse cellular events associated with tumor initiation, promotion and progression. 1 Most of the antitumor activity of Res has been discovered through in vitro studies in tumor cell lines. In these studies, Res was generally found to induce growth inhibition and apoptosis of a panel of human and murine tumor cell lines. [2][3][4][5][6][7] Fewer studies have been conducted on the antitumor effect exerted by in vivo supplementation with Res. Res was found to inhibit tumorigenesis in a mouse skin cancer model. 1 In other studies, it protected rats from ascites hepatoma 8 and colon carcinogenesis 9 and exerted inhibitory effects on tumor growth and lung metastasis in mice bearing highly metastatic Lewis lung carcinoma. 10 In the latter study, the effect of Res was related to its proapoptotic and antiangiogenic action on tumor cells, with no evidence of modulation of the immune response. 10 Res also inhibited the growth of experimentally implante...

Background/Aims: Head and neck squamous cell carcinoma (HNSCC) ranks sixth worldwide for tumor-related mortality. A subpopulation of tumor cells, termed cancer stem cells (CSCs), has the ability to support cancer growth. Therefore, profiling CSC-enriched populations could be a reliable tool to study cancer biology. Methods: We performed phenotypic characterization of 7 HNSCC cell lines and evaluated the presence of CSCs. CSCs from Hep-2 cell line and HNSCC primary cultures were enriched through sphere formation and sphere-forming cells have been characterized both in vitro and in vivo. In addition, we investigated the expression levels of Nicotinamide N-methyltransferase (NNMT), an enzyme overexpressed in several malignancies. Results: CSC markers were markedly expressed in Hep-2 cell line, which was found to be highly tumorigenic. CSC-enriched populations displayed increased expression of CSC markers and a strong capability to form tumors in vivo. We also found an overexpression of CSC markers in tumor formed by CSC-enriched populations. Interestingly, NNMT levels were significantly higher in CSC-enriched populations compared with parental cells. Conclusion: Our study provides an useful procedure for CSC identification and enrichment in HNSCC. Moreover, results obtained seem to suggest that CSCs may represent a promising target for an anticancer therapy.